Parainfluenza viruses are members of the paramyxovirus group, which also includes mumps and Newcastle disease viruses. Human parainfluenza type 3 (PI3; hemadsorption type 1) virus, which is probably the most common among the parainfluenza viruses, causes severe respiratory disease, particularly in children. Parainfluenza viruses type 1 and type 2 have similar epidemiological patterns and often cause croup in children between 1 and 4 years of age. Antigenic relationships have been reported among parainfluenza viruses types 1-4 and also between parainfluenza and mumps viruses, although limited information has been obtained about the protein components involved.
Attempts to vaccinate children against parainfluenza vital infection with formalin-inactivated virus have been reported in the past, but such preparations did not offer effective protection. The results of subsequent studies concerning immunization against paramyxoviruses tend to indicate that inactivation of the virus by chemical treatment probably destroys some of the important antigenic sites responsibe for induction of a protective immune response.
Immunization against respiratory tract pathogens has also been proposed using a modified live virus. Administration of attenuated virus has been attempted intranasally as well as through more conventional routes e.g. subcutaneously, intraperitontally, intramuscularly or intravenously. The elicitation of an immune response through intranasal administration of attenuated virus cannot be considered unexpected in such cases, because the modified live virus of the vaccine is following the natural route of infection of the wild-type virus, creating immunity through a sub-clinical infection. The use of modified live virus to effect immunization entails certain risk, however, in that the avirulent but still active virus may revert to its virulent state after administration to the recipient.
It has previously been documented that envelope glycoproteins, HN and F, of paramyxoviruses are responsible for initiation and progress of the infection process. Studies have shown that antibodies to these glycoproteins are effective in preventing infection.
We previously reported the discovery that a new vital subunit vaccine derived from human parainfluenza type 3 virus envelope glycoproteins complexed with lipid is capable of inducing an antibody response which is far superior to that obtained with the previously used formalin-inactivated vital vaccine preparations. Ray et al., J. Infect. Dis., 152: 1219-30 (1985). Studies conducted using this new subunit vaccine have shown that a single subcutaneous immunization affords complete protection from challenge infection. Id. It was also found that the isolated vital glycoprotein subunit vaccine, composed of a glycoprotein-lipid complex vesicle, was easier to prepare, as compared with subunit vaccines heretofore proposed. The latter are typically isolated in such a way as to be rendered lipid free. See, for example, U.S. Pat. Nos. 4,344,935, or 4,356,169 and More in et al., J. Gen. Virol, 64: 1557-69 (1983). That a glycoprotein lipid complex has shown such exceptional ability to confer immunity is considered quite surprising, as lipids are generally regarded as non-antigenic and thus their presence in a vaccine composition would be thought to reduce its immunogenic effectiveness.
Our vital glycoprotein subunit vaccine, its method of preparation and method of use are the subject of copending U.S. patent application Ser. No. 798,536, filed Nov. 15, 1985, now U.S. Pat. No. 4,790,987.
The preparation of our subunit vaccine is carried out in such a way that the antigenic sites essential for obtaining the desired antibody response are not chemically altered, with the result that antigenicity is not compromised. Further, our vaccine preparation is free of any vital genome and so avoids the risk of infection. Accordingly, our subunit vaccine offers distinct advantages over chemically inactivated virus and modified live virus vaccines. Insofar as is known, however, intranasal administration of a vital coat subunit vaccine has not been proposed heretofore as an effective means for affording protection against infection. Because subunit vaccines include none of the vital genome, neither clinical nor sub-clinical infection could result from administration of such a vaccine. Thus, the knowledge on which previous intranasal, modified live virus vaccines was predicated would not have suggested that a subunit vaccine such as ours, which is comprised of two envelope glycoproteins and the lipid hi-layer from the virus, could induce immunity by intranasal administration.